Potentiation of Na+-dependent uptake of gamma-aminobutyric acid in mouse brain particles by buffer-mediated proton removal.

A number of buffers showed a remarkable facilitatory effect on the uptake of GABA into a mouse brain microsomal subfraction (P3) at 0 degrees C and pH 7.3 in the presence of 80 mM NaCl. Complete dose-response curves were obtained for 21 buffers, ranging in pKa values from 6.2 to 9.9. The data are consistent with the interpretation that the unprotonated forms of the buffers are responsible for the enhancement of GABA uptake by P3 particles and that this is a result of the removal of protons from a membrane site (or sites) in such a manner as to allow the GABA transporter to function. However, the enhancing effects of the buffers could not solely be attributable to unhindered interaction of protonated membrane sites with unprotonated forms of the buffer. Additional factors related to structures of the buffers and membrane properties which might be importantly operative in the enhancement are discussed.